Hyaluronic acid presents widely in living tissues such as cockscombs, umbilical cords, skin, cartilages, vitreous bodies, joint fluid, and is widely used as a component of cosmetics, medical supplies, and foodstuffs, for example. Also, in recent years, approaches to utilization of chemically-modified hyaluronic acid and low-molecular-weight hyaluronic acid as a component of cosmetics, medical supplies, and foodstuffs have been made. For example, WO 2008/133267 describes cationized hyaluronic acid and a method of producing the same. Also, JP-B-5-77681 describes a method for reducing a molecular weight of hyaluronic acid.
WO2008/133267 describes the method of producing the cationized hyaluronic acid, which comprises reacting hyaluronic acid (average molecular weight: 2,000,000) with a cationizing agent in a basic aqueous medium, dissolving a solid obtained by decantation for removing a liquid to a saline solution, then adding an alcohol to the solution to obtain a precipitate, separating the precipitate by filtration, then washing the precipitate with ethanol for purification, and then drying the separated precipitate. Thus, in order to obtain hyaluronic acid or chemically-modified hyaluronic acid from a process solution the hyaluronic acid or the chemically-modified hyaluronic acid is generally precipitated by adding ethanol to the process solution. However, it is not easy for low-molecular-weight hyaluronic acid (for example, hyaluronic acid having an average molecular weight of 100,000 or less) to precipitate by adding ethanol to the process solution merely, and thus a low recovery rate has been a problem.
Additionally, JP-B-5-77681 describes methods of degrading hyaluronic acid in an acidic aqueous solution, then precipitating hyaluronic acid by adding ethanol to the solution, then separating the precipitate by filtration, and washing each precipitate with ethanol for purification. However, in this method, the recovery rate of the hyaluronic acid is low, and thus more efficient method of producing a low-molecular-weight hyaluronic acid has been desired.